1. Field of the Invention
The invention relates to betulinic-acid containing extracts of the plant family Marcgraviaceae, compositions containing betulinic acid or betulinic acid derivatives, and methods for preventing or treating anxiety using same.
2. Background Information
There is ever-increasing interest in herbal or natural-source remedies or medications. Many individuals would rather use such products than conventional pharmaceutical preparations. Additionally, medicinal substances derived from natural products can provide commercial or industrial opportunities for local populations in areas where medicinal plants grow or are cultivated. Moreover, compounds identified as the active ingredients in natural products form an important basis for pharmaceutical research.
Anxiety is a serious disorder that affects many people. Anxiety disorders can be classified into the following sub-categories: generalized anxiety disorder, panic disorders, phobias, obsessive-compulsive disorders, posttraumatic stress disorder, acute stress disorders and anxiety disorders due to medical conditions, substance abuse and not otherwise specified anxiety (American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders, 4th Edn. (DSM-IV). Washington, D.C.). Anxiety disorders are characterized by three basic components; subjective psychological reports, behavioural responses and physiological responses. A person usually reports subjective feelings of tension, apprehension, dread and expectations of an inability to cope (Alloy, L. B., Jacobson, N. S, & Acocella, J., (1999). Abnormal Psychology: Current Perspectives (pp. 150-172.). McGraw-Hill, Boston Mass.). These feelings can lead the person to behavioural responses as coping mechanisms, such as avoidance of the feared situation, impaired speech and motor functioning, and impaired performance on complex cognitive tasks. Physiological changes are often manifested as well; these include muscle tension, increased heart rate and blood pressure, dry mouth, nausea and dizziness (Weiss, S. R. B, & Uhde, T. W. (1990). Animal models of anxiety. In Neurobiology of Panic Disorder (pp. 3-27). Maryland: Alan R. Liss, Inc.). A natural product, or a pharmaceutical preparation derived from a natural product, would be of great interest in the alleviation of anxiety.
Marcgraviaceae is a plant family common in Costa Rica. Although the use of herbal or plant-based remedies is common throughout South America, to our knowledge, anxiolytic activity of plants of the family Marcgraviaceae, or of extracts or compounds obtained therefrom, has not been reported.
A variety of natural or herbal remedies containing betulinic acid have been described as being useful for treating depression or stress, disorders that differ from anxiety.
For instance, U.S. Pat. No. 5,589,182 to Pater and Tashiro describes a pharmaceutical composition in unit dosage form for treating various diseases including depression. The composition comprises a mixture of aqueous extracts of a number of plants, including extracts of dried seeds of Zizyphus jujuba containing betulinic acid. The compositions can be in the form of a health drink, in which the dried powder or concentrated aqueous solution is mixed with a syrup formula, and carbonated water is added.
The WPI abstract for Japanese Patent No. 57031620 indicates that the patent is directed to the preparation of a sweet to reduce stress when stopping smoking. The sweet is prepared by boiling seeds of gardenia in water, boiling persimmon leaves in water, and then mixing the two solutions with corn syrup. The abstract indicates that the solution of boiled persimmon leaves contains, among other things, betulinic acid, The abstract provides that a dose of about 10 grains per day of the sweet can alleviate stress associated with smoking cessation.
The WPI abstract for Japanese Patent No. 69031593 appears to be directed to a method for preparation of “betulin acid” involving extracting the seeds of Zizyphus vulgaris var. spinosus. The abstract provides that betulin acid is a narcotic with no side effects, and is usually obtained from Betula alba. 
Betulinic acid and various derivatives thereof are known to have pharmacological activity, and the patent literature describes the use of such compounds for the treatment of a range of conditions. However, these generally relate to disorders other than anxiety.
For instance, the use of betulinic acid and derivatives thereof for cancer chemoprevention and chemotherapy is described in U.S. Pat. No. 6,048,847 to Jaggi et al., U.S. Pat. No. 6,046,231 to Kosmeder et al., U.S. Pat. Nos. 5,869,535 and 5,658,947 to Dasgupta et al., among others.
Betulinic acid and various derivatives have also been identified as being useful as anti-viral agents. German patent application 19713768 to Draeger et al. discloses a preparation of betulinic acid for use as an anti-cancer and anti-HIV agent. U.S. Pat. No. 5,679,828 also discloses betulinic acid derivatives having anti-retroviral activity, particularly anti-HIV activity.
U.S. Pat. No. 6,124,362 to Bailey et al. identifies betulinic acid as a preferred agent in a composition for regulating hair growth, when applied topically to the scalp.
U.S. Pat. No. 5,529,769 to Cho et al. describes compositions containing betulinic acid said to be useful for the treatment of skin conditions such as wrinkling and photodamage.
Japanese Patent No. 2000-247993 appears to describe a class of triterpenoid compounds including oleanonic acid, oleanic acid, 3-epi-oleanolic acid, betulonic acid and 3-epi-betulinic acid, and indicates that some of these compounds are sigma receptor agonists. The patent appears to conclude that these compounds are therefore useful for the treatment of a broad range of disorders said to be related to the sigma receptor, such as schizophrenia, depression, worry, cerebrovascular disorder, senile activity, Alzheimer's disease, Parkinson's disease, Huntington's disease, drug addiction, stress, anxiety, depression, etc. But no data is presented that the mentioned triterpenoid compounds have any of the recited utilities, let alone anxiolytic activity.